This invention relates to a pharmaceutical composition for treatment of cardiovascular diseases and the method for preparing it. More particularly, it relates to a pharmaceutical composition Huxinkang comprising effective fractions of Complex ShengMaiSan (SMS), a Chinese traditional medicine.
The cardiovascular diseases are common and occur frequently. They are the second diseases, the fatality rate of which is just only next to malignant tumors. Although there has been great improvement in respect of prevention and treatment for cardiovascular diseases, among them myocarditis and myocardosis, especially viral myocarditis, still lack effective medicine for treatment. At present, clinically only means of providing nutrition, coenzyme support and letting patients to take good rest are used. ShengMaiSan is an ancient prescription containing three Chinese traditional medicines of Radix ginseng, Radix ophiopogonis and Fructus schisandrae chinensis, and has been clinically used to treat cardiovascular diseases. The preparation of ShengMaiSan currently is in the form of injection, granule, bags and oral liquid. The methods for preparing it can be divided into three kinds, namely, extracting the 3 medicines separately and then mixing the extractions; decocting the 3 medicines together; and combination of the above two methods. Please refer to Chinese Application for Patent for Invention No. 971071192.6. These methods play significant role in reforming preparations of SMS. However, components of Chinese traditional medicines are complicated, and complex preparations are even more complicated. For example, there are over 10 kinds of components just in Radix ginseng, such as saponins, proteins, polypeptides, amino acids, saccharides, organic acids, alkaloids, terpines, benzedrines, alkynes, lipids, volatile oils, etc. For existing SMS preparation, because the structural kinds of effective fractions are not determined, it is difficult to prepare drugs having definite kinds of main components. Only when kinds of main components are defined, reliable quality standards can be set up. When there are quality standards, stable clinic therapeutic effectiveness can be assured. Only if the quality of products is high, they will be accepted in international market. Therefore, important factors for Chinese traditional medicine to enter international market do not lie in that it has been made in apparently modem forms, such as injection, granule, bags and oral liquid, but in whether the modern forms have definite kinds of main components, whether clinic therapeutic effects of the drugs are stable, and whether there are definite quality standards.
The object of this invention is to provide a pharmaceutical composition for treatment of cardiovascular diseases, especially for viral myocarditis and expansile myocardosis. The composition has definite kinds of main components of Chinese traditional medicines.
The further object of this invention is to provide a pharmaceutical composition having definite kinds of main components, reduced dosage, better purity and quality, stable clinic therapeutic effects, and definite quality standards. The composition has effective fractions of the Chinese traditional medicines.
The further object of this invention is to provide a method to prepare the pharmaceutical composition by decocting the herbs together and then extracting different effective fractions.
The further object of this invention is to provide a method to prepare a pharmaceutical composition according to the combination of properties of the three medicines in Chinese ancient prescription of SMS, and molecular weights of active substances. The pharmaceutical composition has effective fractions of the three Chinese traditional medicines with definite kinds of main components.
The technical solution of this invention is a pharmaceutical composition for treatment of cardiovascular diseases, which mainly contains polysaccharides, saponins and amino acids extracted from Radix ginseng, Radix ophiopogonis and Fructus schisandrae chinensis.
The above mentioned cardiovascular diseases mainly include viral myocarditis, expansile myocardosis, angina pectoris caused by coronary heart diseases, myocardial ischema, heart failure and arrhythmia.
The technical solution of this invention also includes a method to prepare the pharmaceutical composition for treatment of the above mentioned cardiovascular diseases. The method contains the following steps: Radix ginseng, Radix ophiopogonis and Fructus schisandrae chinensis are decocting together with water; water extract or eluate is precipitated by adding ethanol or acetone, treated with macroporous adsorption resin and then with ion exchange resin, and separated to obtain the pharmaceutical composition containing effective fractions of polysacchrides, saponins and amino-acids; and preparation is formed.
Particularly, the method for preparing the above mentioned pharmaceutical composition used for treating cardiovascular diseases contains the following steps:
Radix ginseng, Radix ophiopogonis and Fructus schisandrae chinensis in weight ratio of 1-5 1-3 1-3 are extracted with water;
after the water extract is concentrated, ethanol is added thereto so that the content of alcohol reaches 60%-80%;
polysacchrides are obtained by drying the ethanolic precipitate;
after ethanol is recovered the supernatant is treated with macroporous adsorption resin, first washed with de-ionized water until there is no sacchride, and then with 70%-80% ethanol until there is no saponin, and saponins are obtained from the recovered ethanolic eluate, wherein said macroporous adsorption resin can be D101, S-8 or D3520, among them D101 is preferred;
the water eluate is treated with cation exchange resin and eluated with 2%-15% arnmonia solution to obtain amino acids, wherein said cation exchange resin can be for example 732 cation exchange resin; and the polysacchrides, saponins and amino acids are mixed.
The water extract mentioned in the above method can also be placed on macroporous adsorption resin column after concentrated, here first washed with water and then with ethanol. The ethanol solution is recovered to obtain saponins. After concentrated the water eluate is precipitated by adding alcohol. Polysacchrides are obtained from the alcoholic precipitate. After alcohol being recovered the supernatant is placed on cation exchange resin column and washed with ammonia solution to obtain amino acids. Then the polysacchrides, saponins and amino acids are mixed.
The water extract mentioned in the above method can also be placed on cation exchange resin column, and first washed with water and then with ammonia solution. Amino acids are obtained from ammonia eluate. After concentrated the water eluate is placed on macroporous adsorption resin column and first washed with water and then with alcohol. Saponins are obtained from alcoholic eluate. After concentrated the water extract is precipitated by adding acetone to get polysacchrides. Then the polysacchrides, saponins and amino acids are mixed.
After the polysacchrides, saponins and amino acids are mixed, SMS extract is obtained. It can be mixed with any pharmaceutically acceptable auxiliary material to formulate into various forms, which can be fine granule, granule, capsule or tablet.
The separated effective fractions of polysacchrides, saponins and amino acids are determined qualitatively with conventional test reagents, for example, with anthrone reagent, thin-layer chromatography, and ninhydrin reagent respectively.
Yield range of effective fractions are: polysacchrides 2.77%-8.33%, saponins 1.29%-2.53%, and amino acids 1.04%-1.49%.
There are 20 kinds of amino acids in the obtained amino acids. The content of arginine is up to 5.029%. The contents of alanine, aspartic acid and xcex3-amino butyric acid are also high.
The main features of this invention lie in:
1. The pharmaceutical composition contains mainly polysacchrides, saponins and amino acids extracted from Radix ginseng, Radix ophiopogonis, and Fructus schisandrae chinensis. It is an effective medicine for treatment of cardiovascular diseases, especially viral myocarditis and expansile myocardosis.
2. This kind of pharmaceutical composition containing mainly polysacchrides, saponins and amino acids extracted from Radix ginseng, Radix ophiopogonis, and Fructus schisandrae chinensis has definite kinds of components and stable clinic therapeutic effects. It is easy to set up quality standards and to comply with requirements of international market.
3. This invention provides a preparation method, wherein a group of herbs are decocted together and then different effective fractions are extracted. xe2x80x9cA group of herbs are decocted togetherxe2x80x9d inherits theory and tradition of Chinese traditional medicine, and features of decoctum of Chinese traditional medicine are retained. xe2x80x9cDifferent effective fractions are extractedxe2x80x9d makes kinds of components clear, dosage reduced, and purity and quality improved.
4. The object of this invention also lies in that a pharmaceutical composition mainly comprising polysacchrides, saponins and amino acids is prepared according to the combination of three medicines in an ancient prescription SMS as well as molecular weight of active substances by using macroporous adsorption resin and cation exchange resin. Non-effective components such as mono-sacchrides, inorganic salts, pectin and resins are removed. Compared with the corresponding water decoctum, the dosage is reduced from 60% to 10% by weight of the raw herbs.
5. This invention proves for the first time that the polysacchrides, saponins and amino acids contained in Radix ginseng, Radix ophiopogonis, and Fructus schisandrae chinensis have protection effect to experiment animal model of viral myocarditis, which is accomplished by modulating immunity functions of organism. In addition, pharmacodynamic test shows that the comprehensive drug effects, when polysacchrides+saponins+amino acids are administered to patients jointly, are better than those when the three effective fractions are given separately. The effects are also better than when only two effective fractions of polysacchrides+saponins are administered jointly. Results observed under optic microscope show that SMT 22g/kg (by weight of raw herbs) significantly improve the pathologic change of myocardium caused by virus. Results observed under electronic microscope show that different parts of myocardium striped myofibril and appearance of mitochondria keep intact in the control group, while in the model group, damage to mitochondria is significant, having an appearance of absence. After part of mitochondria disappear, there are oviform void regions left. Muscular fiber was compressed and distorted due to swelling of mitochondria. Striped muscle tendon dissociated. While for the groups administered with the drug, the appearance of mitochondria is uniform, advantitia and spinal meninges systems can be seen clearly, and intact myofibril distributes evenly with every part being distinguished clearly. For the groups administered with SMS water decoct (SMS) or a mixture SMT of polysacchrides, saponins and amino acids, part of mitochondria have a shape of coacervation, and the damage is least. For the groups where polysacchrides, saponins and amino acids are administered separately, degree of damage is greater than the groups to which SMS and SMT are administered, with the phenomena of crista swelling of mitochondria, void regions in mitochondria and the likes occurring.